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29 December 2015 : Laboratory Research  

Niacin Suppresses Progression of Atherosclerosis by Inhibiting Vascular Inflammation and Apoptosis of Vascular Smooth Muscle Cells

Gang SuADEF, Guangli SunADEFG, Hai LiuBCD, Liliang ShuBCD, Jingchao ZhangBCD, Longhui GuoBCF, Chen HuangBCF, Jing XuBCF

DOI: 10.12659/MSM.895547

Med Sci Monit 2015; 21:4081-4089

Abstract

BACKGROUND: Niacin is a broad-spectrum lipid-regulating drug used for the clinical therapy of atherosclerosis; however, the mechanisms by which niacin ameliorates atherosclerosis are not clear.

MATERIAL AND METHODS: The effect of niacin on atherosclerosis was assessed by detection of atherosclerotic lesion area. Adhesion molecules in arterial endothelial cells were determined by using qRT-PCR and Western blot analysis. The levels of serum inflammatory cytokines in ApoE–/– mice were detected by using ELISA. We detected the expression levels of phosphorylated nuclear factors-kB (NF-κB) p65 in aortic endothelial cells of mice using Western blot analysis. Furthermore, we investigated the anti-inflammation effect and endothelium-protecting function of niacin and their regulatory mechanisms in vitro.

RESULTS: Niacin inhibited the progress of atherosclerosis and decreased the levels of serum inflammatory cytokines and adhesion molecules in ApoE–/– mice. Niacin suppressed the activity of NF-κB and apoptosis of vascular smooth muscle cells (VSMCs). Furthermore, niacin induced phosphorylated focal adhesion kinase (FAK) and FAK inhibitor PF-573228 reduced the level of Bcl-2 and elevated the level of cleaved caspase-3 in VSMCs.

CONCLUSIONS: Niacin inhibits vascular inflammation and apoptosis of VSMCs via inhibiting the NF-κB signaling and the FAK signaling pathway, respectively, thus protecting ApoE–/– mice against atherosclerosis.

Keywords: Apolipoproteins E - metabolism, Animals, Apoptosis - drug effects, Atherosclerosis - pathology, Cell Adhesion Molecules - metabolism, Cells, Cultured, Cytokines - blood, Inflammation - pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular - pathology, NF-kappa B - metabolism, Niacin - pharmacology, Signal Transduction, Tumor Necrosis Factor-alpha - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750